Sensitizing drug-resistant cancer cells from blood using microfluidic electroporator

Area of Science:

• Oncology
• Biotechnology
• Microfluidics

Background:

• Directly assessing patient cancer samples offers significant potential for personalized treatment.
• Circulating tumor cells (CTCs) from liquid biopsies are valuable for real-time tumor analysis but lack routine functional interrogation methods.
• Current limitations hinder the clinical translation of liquid biopsies for functional assays.

Purpose of the Study:

• To develop and validate a microfluidic workflow for the functional assessment of circulating tumor cells (CTCs) from liquid biopsies.
• To enable direct drug response assays on purified CTCs for real-time tumor information.
• To overcome the bottleneck in the clinical application of liquid biopsies.

Main Methods:

• A microfluidic vortex-assisted electroporation system was designed for CTC functional assessment.
• Drug response assays were performed on wild-type and drug-resistant non-small cell lung cancer (NSCLC) cells.
• An automated single-cell image fluorescence intensity algorithm characterized electroporation conditions for multi-agent delivery.

Main Results:

• The microfluidic system successfully purified drug-resistant HCC827 GR6 cells from blood with high purity.
• Electroporation conditions were optimized for sequential multi-agent delivery into cancer cells.
• The workflow demonstrated accurate prediction of drug combinations to restore gefitinib sensitivity in resistant cells.

Conclusions:

• This microfluidic multi-drug screening panel workflow enables in situ functional interrogation of patient CTCs.
• The developed system accelerates the clinical standardization and translational use of liquid biopsies.
• This approach facilitates real-time functional analysis of CTCs for personalized cancer therapy.